Adenylate Cyclase-Mediated Modulation of Interaction between Excitatory and Inhibitory Synaptic Influences on Smooth Muscles

We found that nonadrenergic inhibitory synaptic potentials (ISP) induced by intramural stimulation in atropine-treated smooth muscles of the guinea-pig large intestine demonstrated no changes upon the influence of an activator of adenylate cyclase, forskolin. This indicates that cAMP-dependent pathways are not involved in the generation of ISP. However, in these muscles with no atropine pretreatment ISP were suppressed by forskolin; intramural stimulation evoked in these smooth muscle cells M-cholinergic excitatory synaptic potentials (ESP) instead of ISP. An increase in the intracellular cAMP concentration due to application of its membrane-penetrating form, dibutyryl-cAMP, did not mimic the above-described effect of forskolin. Hence, it can be supposed that the effect of forskolin on inhibitory synaptic transmission in the atropine-untreated smooth muscles is not related to changes in the intracellular cAMP level; this effect is determined by other mechanisms. The above differences between the effects of forskolin on ISP in the atropine-treated and atropine-untreated smooth muscle strips indicate that the interaction of intracellular signal pathways (probably, through protein G(q/11)), which is observed with activation of adenylate cyclase, occurs under conditions of simultaneous activation of. cholinoreceptors and purinoreceptors. The pattern of adenylate cyclase-mediated modulation of inhibitory effects of purinergic neurons on smooth muscles does not allow us to rule out the possibility of involvement of interstitial cells of Cajal as a relay link providing this synaptic effect. Transmission of excitation from cholinergic nerve terminals to smooth muscles is realized without the participation of the interstitial cells of Cajal.